Juvenile Idiopathic Arthritis

Disease/ Disorder

Definition

Juvenile idiopathic arthritis (JIA), previously known as juvenile rheumatoid arthritis (JRA) or juvenile chronic arthritis (JCA) is a form of arthritis (i.e., swelling or limitation in range of movement of a joint with warmth, pain or tenderness) of unknown etiology that occurs for at least 6 weeks in children younger than 16 years of age.¹ Thought to be a multifactorial autoimmune disease with unknown exact cause, it can continue into adulthood, causing significant disability, poor functional outcomes, and decreased quality of life.²

Etiology

The definitive cause of JIA remains under investigation; however, current research indicates that genetic, immunogenic and environmental factors influence the development of JIA subtypes. Genetic association varies between the disease subtypes. Non-systemic variations of JIA are more likely to be associated with the human leukocyte antigen (HLA) class.^3,4HLA-A2 & HLA-B27 are implicated in certain forms off JIA, especially in subtypes with earlier onset.

Developing genetic research is focused on the use of genome-wide association studies and transcriptome-wide association studies to identify genes associated with JIA.  Most recently, a study identified several novel genes that may be implicated in the development of disease, ANXA3, GPR146, ANKRD9, and TMEM158. While this has improved our understanding of genetic correlations with disease development, conclusive causation remains under investigation.⁴

In addition to HLA genetic associations, non-HLA genes also play a role in the inflammatory response in certain JIA subtypes, with involvement of both cell-mediated and humoral-immunity. Multiple genes relating to inflammation and immune regulation are believed to be involved, including those that influence TNF, IL2, IL10, IL6 and other inflammatory regulators.² There is evidence of autoimmune dysregulation, with positive antinuclear antibody (ANA) in 40% of patients. However, evidence from treatments designed to block the inflammatory cascade indicate that systemic inflammation may play a greater role.

While there are studies that strongly indicate a genetic component, studies with monozygotic twins have elucidated that environmental factors, such as infections, also play a role. Concordance rates are closer to 25-40% (as opposed to 100%) in these twins.⁵ Repeated infections and antibiotics during the first two years of life are associated with JIA in multiple studies.² The most commonly implicated pathogens include Parvovirus B19, Epstein-Barr virus, enteric bacteria, Chlamydia species, Bartonella henselae, Mycoplasma pneumoniae, and Streptococcus pyogenes. External antigens may provoke multiple antigen-specific pathways, including cytotoxic T-cell responses, proinflammatory cytokine production, and the complement cascade, increasing the risk of immune-mediated arthritis during childhood.² However, it is unclear whether this is due to pathogenic alterations of the microbiome or changes to our immunologic cells.

Epidemiology including risk factors and primary prevention

JIA is the most common connective tissue disease in children.¹ It is currently estimated that JIA may be highly heritable and associated with multiple autoimmune disorders.^6,7 0.07 to 4.01 per 1000 children are affected worldwide. The average yearly incidence is approximately 13.9 cases per 100,000 with a prevalence of 16-150 cases per 100,000 people.¹ Child onset accounts for 5% of RA cases.  Differences in age and sex can also be seen within subtypes of JIA.^1,2 For example, in rheumatoid factor (RF) positive JIA, females may outnumber males 9:1 compared to overall JIA ratios. Systemic features of JIA appear to be more common in pediatric than adult onset arthritis. Children are most likely to experience synovitis whereas adults predominate with earlier joint destruction.¹

Recent epidemiologic surveys have shown distinctions in geography and ethnic groups. Oligoarthritis is predominant in western countries but rare in areas such as India, South Africa, and the Middle East, where the polyarticular form of JIA is more common. Greater incidences of enthesitis-related arthritis are present in India, Taiwan, parts of Mexico, and Canada. Black Americans have a higher rate of RF positive polyarthritis whereas European ancestry may predispose children to higher rates of ANA positive JIA.⁸

A multinational study, named the Epidemiology, Treatment, and Outcome of Childhood Arthritis (EPOCA Study), is currently ongoing to obtain epidemiologic data on JIA subtypes. Preliminary data shows a younger age of onset in Western Europe and a higher prevalence of uveitis in this population. While there may be lower rate of incidence in Asian populations, there may be higher rates of systemic arthritis in these patients. Thus far, children in Africa and Eastern Europe have been found to have higher levels of disease activity as well as a lower frequency of inactive disease.⁹ Our understanding of the etiology of JIA continues to evolve to this day.

Patho-anatomy/physiology

JIA is an inflammatory syndrome characterized by chronic synovial inflammation with B-lymphocytes. Macrophage and T-lymphocyte invasion occurs along with cytokine release and further synovial proliferation. There is a major pathogenic role for the overproduction of interleukin-6 and interleukin-1.^2,6 Eventually, the thickened synovium (pannus) contributes to joint destruction. Within the synovial fluid itself, interleukin-18 expression has consistently been found to be abnormal.

The subtypes of juvenile arthritis can be differentiated from one another based on the number of affected joints, underlying biochemistry, and the presence of associated comorbidities. Subtypes are classified using the International League of Associations for Rheumatology (ILAR); however, there is an ongoing study through the Pediatric Rheumatology Internal Trials Organization (Printo) currently working on new classification criteria.¹¹

JIA Subtypes^1,10,11,12

• Oligoarticular
  • Persistent oligoarthritis: affecting fewer than four joints throughout the course of the disease
  • Extended oligoarthritis: affecting two to four joints during first six months of disease but greater than five joints after six months of disease
  • ANA + lab result in 70-80% of patients
  • Onset: early childhood, In children under 6 years old, Females > Males
  • Most common subtype, 40-50% of children with JIA,¹ best prognosis
  • Larger lower extremity joints often with asymmetric arthritis presentation, especially knees, most commonly affected
  • Asymmetric uveitis often develops within first 4 years
    • Require routine eye examinations
  • Ocular damage is common, 50% develop chronic iridocyclitis

• Polyarticular
  • Affects five or more joints during the first six months of disease
    • Symmetric involvement of small joints of hands and feet
    • Cervical spine and temporomandibular joint (TMJ) may be affected
  • Two subtypes:
    • Rheumatoid factor (RF) negative polyarthritis: More often, patients complain of stiffness versus pain
      • Typically presents with symmetric small joint involvement and severe inflammation
        • Hip involvement 50% of cases, can lead to late disability with erosion of the femoral head
      • 18-30% of JIA Patients
      • Positive ANA in 20-40% of patients
    • RF positive polyarthritis: Less than 5% of all JIA cases, with 50% developing severe arthritis
      • Variable prognosis, more aggressive disease course
      • May have positive antibodies to cyclic citrullinated peptides (anti-CCP)⁸
  • ANA+ in 25%-40% of cases
  • Onset: RF positive in late childhood, RF negative is often younger than six years; Females > Males
• Systemic
  • Arthritis in one or more joints with or preceded by fever of at least two weeks duration and daily fever (for at least three days), and accompanied by at least one of the following signs: non-fixed erythematous skin rash, generalized lymph node enlargement, hepatomegaly or splenomegaly, serositis
  • 5-8% of children develop macrophage activation syndrome (MAS)¹
  • 10% of JIA patients
  • Onset: any age, Female = Males
  • Quotidian pattern of high spiking fevers
  • Rash is evanescent, salmon colored, macular, accompanies fever
    • 10%-20% develop acute iridocyclitis
  • Arthritis occurs later, a month or longer
  • Formerly known as Still’s Disease or systemic juvenile rheumatoid arthritis
• Psoriatic
  • Arthritis and psoriasis with at least two of the following: dactylitis, nail pitting or onycholysis, psoriasis in a first-degree relative
  • 5-10% of patients
  • Onset: biphasic with early peak younger than six years, late peak after six years of age, females =male
• Enthesitis-Related
  • Enthesitis at the sites of tendon insertion on to bone with at least two of the following:
    • presence or history of sacroiliac joint tenderness or lumbosacral pain
    • HLA-B27 antigen positive
    • onset of arthritis in male over six years of age
    • acute symptomatic anterior uveitis
    • history of ankylosing spondylitis
    • enthesitis-related arthritis
    • sacroiliitis with inflammatory bowel disease
    • acute anterior uveitis (Reiter’s syndrome) in a first-degree relative
  • Occurs in 15-20% of JIA patients
  • Most common sites: calcaneal insertion of Achilles tendon, plantar fascia, tarsal area
  • Most common age of onset is 10 years of age
  • Complications include
    • In 30-40% of patients with this type of JIA, disease progresses to affect sacroiliac joint
    • Uveitis is common: often symptomatic and unilateral
    • Can also progress to spondyloarthropathy
  • Onset: late childhood, commonly after 6 years old, Males > Females
    • Positive Family Medical History may be present
• Undifferentiated
  • 5% of JIA subtypes
  • Male = Female
  • May meet none or many criteria of other JIA subtypes

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Variable dynamic disease progression is seen in the first six months from onset of JIA.⁶ Patients may experience a cycle of remission and flare ups of symptoms. In a 30 year longitudinal cohort study, it was noted that 59% of JIA patients were in remission (defined as no disease activity and the absence of medications for at least 6 months) at the 30 year follow up; however, 28% of patients in this cohort were still experiencing a heavy symptom load.¹³ RF positive JIA appears to have lower levels of remission compared to other subtypes of JIA.

As children grow into adulthood, previous studies have noted the presence of severe disability in as many as 42.9% of patients; however, more recent publications have noted significantly lower rates of severe disability (3-8.9%) with the highest disability rating in RF+ polyarticular disease. ¹⁴ Currently, the best predictor of long standing high disability ratings depends on level of disability at initial presentation. While modern understanding is improving identification and treatment for JIA patients, there are still concerns for long term complications, including mental health concerns.¹⁵ Standardized mortality ratios are higher in both male and female patients with JIA when compared to the general population. Likewise patients with systemic JIA had higher mortality incidence when compared to non-systemic subtypes of JIA.¹⁶

• New onset/acute:
  • Each JIA subtype has varying symptoms; however, all subtypes share several traits:
    • Persistent joint pain, swelling, warmth, and stiffness
    • Symptoms are worse in the morning or after prolonged rest (nap, sitting still)
  • An early sign is the presence of a limp or altered gait
    • A younger child may not verbalize pain, but demonstrate limping or gait alterations if one or both legs are involved
• Subacute: For some patients with JIA, the course of disease may have episodic flare ups followed by asymptomatic periods. It is important to recognize that remission is currently recognized as a period of 6 months without evidence of disease and without medications to mitigate the disease.    
• Chronic/stable: Complete remission can be expected in most patients, with current estimations at 67% of patients at eight years in remission given new treatment and early diagnosis.¹⁸
• Remaining patients continue to have symptoms into adulthood, requiring long term medical management and follow up.
• Pre-terminal: Only in very severe cases, affecting cervical spine or causing significant debility.

Specific secondary or associated conditions and complications

• Anorexia, weight loss, growth failure
• Cardiopulmonary involvement (pericarditis, pleural effusions with rare complication of tamponade, if large enough)
• Anemia
• Decreased physical activity contributes to weakness, obesity (which increases load on joints)
• Atlantoaxial instability associated with cervical spine involvement increases risk of spinal cord injury
• Concerns have been raised about increased rates of cancer (does not seem to be related to treatment with biologic agents as was once thought)
• Uveitis, specifically iridocyclitis. More common in females affected with oligoarticular arthritis and in patients less than six years of age with a positive ANA. Usually asymptomatic, but if not diagnosed early may result in permanent blindness.
• Growth disturbances, including growth retardation and accelerated growth, resulting in conditions such as leg length discrepancies
• Micrognathia if TMJ arthritis disturbs the growth plate (particularly in polyarticular JIA)
• Suppression of the immune system by disease modifying antirheumatic drugs (DMARDs) increases the risk of infections
• Osteopenia and osteoarthritis
• Fractures
• Hepatomegaly, splenomegaly, lymphadenopathy (particularly in systemic JIA subtype)
• Rare pulmonary manifestations may include interstitial lung disease or pulmonary hypertension¹⁹
• Macrophage Activation Syndrome (MAS) resulting from uncontrolled activation and proliferation of T-lymphocytes and macrophages is a complication with systemic JIA. It is a life-threatening condition resulting in persistent fever, pancytopenia, hepatosplenomegaly, and coagulopathy.
• Other autoimmune conditions, four have been associated with JIA
  • Rheumatoid arthritis, Celiac Disease, Hypothyroidism, Systemic Lupus Erythematosus⁶
• Pain is an incredibly common symptom. JIA patients with symptomatic pain are at higher risk of developing Chronic Amplified Pain Syndrome

Essentials of Assessment

History

• Joint pain and swelling, often noted incidentally after trauma
• Stiffness worse in morning or after naps and lasts more than fifteen minutes
• Symptoms better later in the day
• Persistence of symptoms for at least six weeks in a six-month period
• History of fever without other cause, in absence of joint symptoms; may be three days, with a double spike pattern of high temperatures
• Child refusing to walk, or using hands to walk
• Pain with ambulation, “gelling” sensation (stiffness after a joint remains in one position for a prolonged period), joint swelling, and difficulty with buttons or writing
• Photophobia, pain, redness, headache, and visual changes
• Isolated musculoskeletal pain is generally not JIA
• Detailed family medical history^1,7

Differential diagnoses include: Perthes disease, slipped capital femoral epiphysis (SCFE), malignancy (osteosarcoma for joint pain, leukemia for fever combined with joint pain, lymphoma), ankylosing spondylitis, inflammatory bowel disease, septic arthritis, Kawasaki disease, malaria

Physical examination

• Musculoskeletal:
  • Painful, swollen joints
  • Tenosynovitis>Bursitis
  • Number of joints
    • 2-4: Oligoarticular
    • 5 or more: Polyarticular
    • Any joint can be affected, including small joints of the fingers, sternocostal, vertebral joints (including cervical), and the jaw. Knees, wrists, and ankles are more affected in polyarticular.
    • Note if deformity presents with chronic disease.
  • Range of motion: May be decreased. Note if contractures. May see cervical spine involvement
• Extremities: limb length discrepancy. Systemic disease may present with lymphadenopathy. Children are more likely to present with ulnar deviation and loss of extension. Radial deviation may occur at the MCP joints with finger flexion
• Gait: antalgic limp
• Head, eyes, neck: Check eyes for uveitis in girls with positive ANA and oligoarticular JIA. Receding chin from early ossification of the mandible (micrognathia)
• Skin: evaluate for rashes. Document type and location.
• Gastrointestinal: systemic disease may have hepatomegaly and/or splenomegaly
• Cardiovascular: may have pericarditis, myocarditis (muffled heart sounds, pericardial friction rub)

Functional assessment

• Juvenile Arthritis Disease Activity Score (JADAS): measures count of joints actively involved, physician assessment of disease and patient functionality, parent or patient assessment of wellbeing²¹
• Childhood Health Assessment Questionnaire (CHAQ) Disability Scale: measures activities of daily living (ADL) and independence
• Juvenile Arthritis Self-Report Index: measures self-care, mobility, school and extracurricular involvement
• Juvenile Arthritis Functional Assessment Report (JAFAR): focuses on performance of physical tasks, has parental and self-report versions
• Health-Related Quality of Life (HRQoL): used as a measure of functional outcome and to measure responses to treatment. Includes scores for:
  • Psychological Functioning (MCS)
  • Physical Functioning (PCS)²²
• Health Utility Index Mark 3 (HUI3) and the Medical Outcomes Short Form 36 (SF-36) have been utilized to assess functional improvement in patients with JIA²²
• Patient-Reported Outcomes Measurement Information System (PROMIS): includes functional measures such as mobility, upper extremity function, fatigue, and pain interference²³
• ACR Pediatric response criteria: measures disease activity through physician assessment and patient/parent assessment of functional ability, overall wellbeing, number of joints affected as an outcome measurement of treatment²¹

Laboratory studies

No specific laboratory studies definitively diagnose JIA, thus highlighting the importance of a comprehensive history and physical examination. Blood testing for inflammatory markers (Erythrocyte sedimentation rate, C-reactive protein) and autoimmune markers (RF, HLA-B27, ANA) are recommended

• RF-positive in 3%-5% of polyarticular subtype
•  ANA positive in 80% of oligoarticular subtype, associated with uveitis
•  Serial trending of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) help gauge effectiveness of treatment
•  Complete blood count (CBC) to evaluate for anemia of chronic disease and leukocytosis
• Other autoantibody testing to consider and may prove beneficial
  • anti-MCV, anti-CCP helpful in diagnosing early disease²⁴
• Joint aspiration to rule-out septic arthritis
• Hyperferritinemia may be found in systemic JIA²⁶

Imaging

Plain films, magnetic resonance imaging (MRI), and ultrasound can be used to detect joint changes.

• Plain films: periarticular soft tissue swelling, overgrown or ballooned epiphyses, periostitis
  • Later, may show erosive disease, joint space loss
  • Periarticular bone demineralization radiographically once at 50% demineralization
• MRI: high sensitivity to detect bone damage and damaged cartilage
• Ultrasound: Noninvasive tool useful for assessing number of joints involved and differentiating between tendon and articular involvement without radiation²⁵
• Dual-energy x-ray absorptiometry (DEXA): to identify osteoporosis
  • Particularly useful in patients requiring long term corticosteroids or those with decreased levels of physical activity

Supplemental assessment tools

• Physician and parent global assessments of overall disease activity
• Juvenile Arthritis Multidimensional Assessment Report (JAMAR): focuses on global health of patient with JIA, including overall wellbeing, pain, functional status, quality of life, joint and extra-articular or systemic involvement, medication, treatment compliance²¹
• Steinbrocker functional classification rates the extent of physical disability in patients^27,28

Early predictions of outcomes

• Overall poorer outcomes and higher disability associated with increased disability at initial presentation
• Poorer prognosis associated with:
  • Hip or cervical spine involvement, joint space erosion, positive RF, and positive anti-CCP antibodies
  • Early hand involvement and radiographic changes of carpal length are also associated with poorer prognosis
  • Systemic and polyarthritis with RF positivity have the highest incidence of advanced joint damage and long-term disability
  • Inactivity and poor aerobic and musculoskeletal fitness. Affected children are at an increased risk of cardiovascular disease, diabetes mellitus, depression, hypertension, obesity, osteoarthritis/osteoporosis²⁹
• Positive ANA may be associated with less disability¹
• Early intensive therapy in JIA may improve long term disease outcomes, including prevention of cumulative joint damage

Environmental

• More severe cases may require home modifications, including ramps and roll-in showers secondary to mobility limitations
• Changing doorknobs to handles may help those with advanced hand and wrist involvement
• School accommodations based on Section 504 of the Rehabilitation Act
  • Regulations to accommodate decreased ability to get from class to class, take notes, or carry books
  • Provision of modified school supplies may be necessary, if small joints of hands and grasp affected
  • Recommendations for physical education modifications to assist in maintaining student activity, provide joint protection, and energy conservation techniques

Social role and social support system

• Data indicates that adolescents with JIA struggle with physical vulnerability, isolation, and managing uncertainty. Many find resilience through taking control of their disease. Sharing of experiences with other adolescents can help foster acceptance and self-growth.³⁰
• Family frustration due to delay of diagnosis in some cases
• Pain leads to missed school and participation
• Quality of life indices for patients were found to decrease with psychological distress, higher disease activity, or when their caregivers reported financial hardship³¹

Professional Issues

Physiatrists must be strong patient advocates in multiple settings, including school, home, and community environments. Sensitivity to patients’ cultural background, ethnicity, gender, age, religious beliefs, and sexual orientation is paramount to building trust across the spectrum of care. Patient safety issues include minimizing medical errors, addressing medication side effects, and providing a safe environment at home and during therapy.

Rehabilitation Management and Treatments

Available or current treatment guidelines

• 2019 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis
  • 2021 guideline updates provided for several types of JIA¹⁸
• 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging³²
• American College of Rheumatology Guideline for the Treatment of JIA Oligoarthritis, TMJ, sJIA Guideline, 2021³³

At different disease stages

New onset/acute

• Early intervention focuses on symptom relief through medication and physiotherapy and adopting adequate lifestyle changes.
  • Rest, Splinting, Passive Range of Motion (ROM), Strengthening Exercises, Adaptive Equipment, Functional Training
• First-line medications
  • Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and decrease of inflammation (typically see improvement in first 1-3 days):³⁴
    • Diclofenac
    • Naproxen
    • Ibuprofen
    • Indomethacin
    • Meloxicam
    • Tolmetin
  • Intra-articular steroid injections with triamcinolone hexacetonide is preferred for children
  • For uveitis, topical corticosteroids followed by systemic corticosteroids or biologics in resistant cases (such as Infliximab)
• Second-line medications in cases of more severe or refractory acute disease presentation:
  • Include patients with systemic symptoms or severe onset in the acute setting
  • Poor response to NSAIDs
  • IL-6 or IL-1 inhibitors
    • Anakinra
    • Canakinumab
    • Tocilizumab
  • Methotrexate
  • Glucocorticoids: although systemic steroids are being used less frequently in acute settings, refractory or severe cases may still benefit from addition of systemic glucocorticoid use
• Includes rehabilitation strategies that stabilize or optimize function and prepare for further interventions at later disease stages:
  • Gentle range of motion
  • Cold packs applied to joints
  • Supportive orthoses, especially knees and wrists to maintain alignment
  • Shoe modifications to support ankles and feet
  • Appropriate physical activity, based on symptom burden
    • Low impact activities may be beneficial and less aggravating
    • Swimming or cycling
  • Appropriate rest from activities during flares

Subacute

• In ongoing therapy, the treatment remains focused on symptom management through medication and physiotherapy and lifestyle modifications.³⁴
• First line therapy:
  • DMARDs
    • Methotrexate
    • Sulfasalazine: helpful in enthesitis-related disease³²
  • Anti–interleukin (IL)-1 agents include anakinra, canakinumab, rilonacept
  • Anti–IL-6 agent tocilizumab
• Second line therapy
  • TNF-α inhibitors like etanercept, infliximab, and adalimumab help reduce flare-ups
    • Repeated annual screening of TB in low risk patients with a negative initial TB screen is not recommended
  • T-cell immunologic medications such as abatacept³⁴
  • CD-20 antigen suppression agent Rituximab²⁷
  • Anti-tumor necrosis factor drugs in addition to those above
    • May have severe adverse effects, requiring dose adjustments
  • Systemic corticosteroids are becoming less used in initial management of JIA flare ups, reserved for resistant cases^32,34
    • Should be monitored closely as long term steroid use can be detrimental
• Includes rehabilitation strategies to optimize function:
  • Range of motion: passive ROM exercises should NOT be performed in an inflammatory joint
  • Cold: pain relief, increase pain threshold, decrease muscle spasm (vasoconstriction)
  • Heat, including paraffin and beads for hands
    • increases tissue elasticity, reduces stiffness, decreases pain, reduces muscle spasm
    • Superficial heat (hot pack) can provide tissue heat up to one centimeter in depth¹
  • Hydrotherapy: Water temperature between 90-100 degrees Fahrenheit
  • Ultrasound modality generally avoided in children due to controversy over growth-plates
  • Mobilization to prevent debility
  • Joint protection techniques
    • Splinting of the upper extremity: 15-20 degrees of wrist extension, finger flexion, 25% MCP flexion. It is important to control ulnar deviation and thumb abduction¹
  • Adaptive equipment for mobility (walker with forearm supports if grip is too difficult) and ADLs (adapted silverware, pencil or crayons)
  • Adapted computer access

Chronic/stable

• Includes secondary prevention and disease management strategies
  • Monitor cervical spine
  • Supportive orthotics, especially for knees, feet, ankles and wrists
  • Jaw guards for sports if jaw involved
• Includes palliative strategies
  • Supportive nutrition
• Includes symptom relief
  • NSAIDs
  • Appropriate and adequate pain management
  • Complementary and alternative medicine techniques common
• Includes rehabilitation strategies to optimize function
  • Massage
  • Stretching and flexibility
  • Yoga
  • Exercise program including aquatics
    • Aerobics, while protecting joints
    • Strengthening, isometrics may be better for affected joints
  • Participation in sports is not contraindicated
  • Joint protection strategies
  • Environmental adaptations
  • Nighttime resting splints

Joint Pain can be assessed by using the child Visual Analog Scale (VAS) or the Varni/Thompson Pediatric Pain Questionnaire.¹

Refractory disease

• New evidence that allogeneic stem cell transplantation was beneficial in addressing refractory disease.
• Recent study provided evidence that patients who received stem cells after aggressive immunosuppressive therapy had a higher rate of remission; however, comorbidities related to immunosuppressants and stem cell therapies were high³⁵

Pre-terminal or end of life care:

• Severe complications, such as cervical spine involvement can lead to severe disability and early death.
• Includes symptom relief
  • Continued pain relief and supportive care

Lifestyle modifications and education about disease and treatment options at all stages of disease helps with symptom and comorbidity management. New research has indicated the important role of physical activity and nutrition in all patients with JIA, which unfortunately, is lacking in children with JIA who are less likely to be physically active when compared to children without JIA due to symptoms. This lack of activity can cause a multitude of problems, including low muscle development and higher risk for obesity.  A recent study has indicated the benefit of low intensity exercise with adherence in children with JIA.^36,37 Likewise, following a well-balanced diet is imperative for bone health and overall wellbeing. JIA patients are at a higher risk of developing osteoporosis due to inadequate mineral intake and lack of weight bearing activity. It is also suggested that gastrointestinal component of the disease burden as well as possible malabsorption and side effects from various medications impact patients’ nutritional status, so it is imperative to discuss adequate dietary changes to meet each patient’s needs.³⁸

Role of Corticosteroids

The role of corticosteroids is now more limited as methotrexate and other biological agents have become more accessible and better studied. New research has indicated that IL- inhibitors have been more effective with less side effect profile for patients with JIA. While systemic corticosteroids are very useful in refractory cases, they should be used sparingly in patients who respond well to NSAID and DMARD therapy.  However, there are many instances when corticosteroids are indicated.

• Intraarticular Injections: triamcinolone hexacetonide can treat contractures secondary to synovitis to prevent limb length discrepancies or anatomic deformities. Ultrasound guidance can maximize efficacy and prevent subcutaneous atrophy (caused when steroid preparation is delivered out of the joint space). A recent review found that knee joints may benefit from rest, but wrist joints may not benefit from rest following steroid injections.³⁹
• Chronic Iridocyclitis: screen all children periodically for iridocyclitis with slit-lamp examinations as it is asymptomatic at onset and early diagnosis can improve outcomes. Periocular steroid injections can be used if there is no response to topical therapy (first line). Systemic steroids are indicated in localized treatment failure.³⁶
• Corticosteroids as a bridge: short courses of corticosteroids can be used to alleviate pain and stiffness in patients waiting for full therapeutic effects of recently initiated therapies or symptoms refractory to other therapies. ^34,36
• Systemic JIA: one of the main indications for systemic corticosteroids; if symptoms recur after steroid tapering, methotrexate or biologic agents are typically used (anti-IL-1 or anti-IL-6 inhibitors).
• Macrophage Activation Syndrome (MAS): MAS is a life-threatening syndrome that occurs in 6-8% of patients and is a form of reactive hemophagocytic lymphohistiocytosis. MAS is a medical emergency and should be promptly recognized and treated. ¹

Role of Physical Therapy and Exercise

Exercise therapy is well tolerated and beneficial across various outcome measures in patients with JIA. It is considered an integral component of the standard of care for JIA, as children commonly display balance abnormalities, muscle weakness and atrophy, decreased physical fitness, and may be more sedentary regardless of disease activity.⁴⁰ Likewise, bodyweight exercise is imperative for healthy bone development. JIA patients are at an increased risk for developing osteoporosis complications and increased exercise reduces this risk.⁴¹ Growing evidence shows that exercise does not lead to worsening of JIA symptoms. In fact, the evidence shows that a physical therapy led exercise program can have beneficial effects on multiple outcome measures, including the Child Health Assessment Questionnaire, Pediatric Quality of Live Inventory, pain scores, and muscle strength.  Another recent study evaluated the type of physical activity parameters for patients with JIA and determined that low-impact exercise was followed with better adherence by patients, including swimming and cycling.⁴²

In addition, The Ottawa Panel for Evidence-Based Clinical Practice Guidelines for Structured Physical Activity (2017) recommended Pilates, cardio-karate, home and aquatic exercises in order to improve quality of life, pain, functional ability, range of motion, and decrease the number of active joints affected.⁴³

Coordination of care

JIA consists of multiple complex subtypes requiring a multi-disciplinary team working together to ensure that needs are being met. This team can include a rheumatologist, a family practice physician, physical and occupational therapies, a physiatrist, and a mental health expert. Orthopedic surgery may need to be involved if deformities are present. Physiatrists play a large role in managing orthotics and coordinating care with physical and occupational therapies. Likewise, further research on the impact that diet has in autoimmune and inflammatory diseases has indicated that better nutrition management, particularly with an anti-inflammatory diet, is beneficial in symptom management. With this knowledge in mind, dietician or nutritionist support may also be beneficial for educating patients how best to make necessary lifestyle modifications.^40,42,44

Patient & family education

Patients and family members are integral members of the medical team. It is imperative that they remain educated and heard throughout the diagnosis and treatment process. Patients report higher levels of satisfaction with medical management when they are consulted and empowered to make decisions in their own medical care.

Important topics to discuss in patient and family support education include:

• Joint protection
• Energy conservation techniques
• Need for regular range of motion
• Need for maintaining overall health, including nutrition and fitness
• Adequately explain pain regimen and any potential adverse effects
• Educate on activity restrictions and therapy programs
• Patients and families should be aware of complications of the disease or treatments
• Atlantoaxial involvement precludes participation in contact sports, as well as gymnastics and jumping on trampolines, due to risk of subluxation/dislocation causing spinal cord injury
• Weight bearing status
• Recommended medical, surgical, and rehabilitative treatments
• Duration of treatment

Emerging/unique interventions

Impairment-based measurement

• American College of Rheumatology Revised Criteria for Classification of Functional Status in Rheumatoid Arthritis¹
  • Class I: Independent with Activities of Daily Living (ADL)
  • Class II: Independent with self-care and vocational activity (limited avocational)
  • Class III: Independent with self-care (limited vocational and avocational)
  • Class IV: Limited in ability (self-care, vocational, avocational)
• Childhood Health Assessment Questionnaire (Discomfort scale)
• JADAS (Juvenile Arthritis Disease Activity Score): includes physician’s global assessment of disease activity, parent’s assessment of well-being, ESR, and number of joints with active disease. There are also variations of the JADAS score that can be used:
  • JADAS-CRP: replaces ESR with CRP measurement
  • Clinical JADAS (cJADAS): does not include ESR or CRP⁴⁶
• Juvenile Spondylarthritis Disease Activity Index (JSpADA): used to measure disease activity by asking patients to rank certain symptoms (arthritis, enthesitis, pain, acute phase reactants, morning stiffness, clinical sacroiliitis, uveitis, back mobility), with higher scores indicating greater disease activity⁴⁶
• Juvenile Arthritis Damage Index (JADI): quantifies the amount of damage, defined as persistent anatomical changes or functional changes, in order to measure morbidity⁴⁶

Measurement of patient outcomes

• Juvenile Arthritis Quality of Life Questionnaire: physical function and emotional well being
• Juvenile Arthritis Multidimensional Assessment Report (JAMAR) – being used in the EPOCA study⁵
• Juvenile Arthritis Functional Assessment Scale (JAFAS): activity performance and participation^40,44
• Childhood Arthritis Health Profile: physical and psychosocial functioning, and family impact of the disease
• Quality of My Life Questionnaire: focuses on separating problems related to JIA versus other issues
• Childhood Health Questionnaire: general health, pain, physical activity, self-esteem and family issues
• Pediatric Quality of Life Inventory Scales: physical, emotional, social, school function
• Patient-Reported Outcomes Measurement Information System (PROMIS): developed by the National Institutes of Health (NIH) for use across a range of conditions to assess self-reported health and has recently been researched in pediatric JIA²³

Translation into practice: Practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

• Leg length discrepancy related to joint damage due to chronic synovitis of involved lower extremity joint may require orthotic adjustments, including shoe lifts
• Symptom management with intra-articular steroids can decrease inflammation and help prevent synovial overgrowth
  •  Intra-articular steroids into affected joints can be given in conjunction with systemic NSAID therapy in acute presentation
• Exercise should be promoted, even in times of disease flare. Regular low to high intensity exercise, including aquatic therapy, cycling, and weight-bearing activity, has been shown to decrease pain, improve clinical symptoms, and improve quality of life. Likewise, routine exercise reduces risk of osteoporosis development and helps maintain healthy weight
• Patients with JIA are at high risk for chronic pain and early exposure to opioids. Older age of onset, increased disability or decreased function, and longer disease duration have all been associated with higher pain levels. Patients at risk of chronic pain should be identified early and targeted with multidisciplinary pain management interventions in order to improve long term pain outcomes and decrease opioid dependence.
• Overall prognosis in the development of severe chronic disease can be estimated by severity of symptoms at initial presentation
• New research has indicated the importance of dietary habits in the non-Pharmacologic management of auto-immune and inflammatory diseases. Currently, research has indicated that following an anti-inflammatory diet can be very beneficial. Examples include, whole food, plant based and Mediterranean-style diets.

Cutting Edge/ Emerging and Unique Concepts and Practice

• The EPOCA Study is a multinational study coordinated by the Pediatric Rheumatology International Trials Organization (PRINTO). This study is collecting information from over 9000 patients from over 40 countries with the aim to obtain information on frequency and characteristics of JIA subtypes across the globe. Preliminary data is available while the study is currently ongoing.^5,9
• Delayed Gadolinium-enhanced MRI cartilage imaging may be able to assess proteoglycan content within joints before morphological damage is apparent, leading to earlier recognition and treatment of JIA
• Smart devices and technologies, including phone applications, are being explored to monitor symptoms and disease progression, to increase adherence to prescribed medications, and to encourage physical activity. These technologies have been implemented in other diseases previously, such as asthma and adult rheumatoid arthritis.^46,47

Gaps in the Evidence-Based Knowledge

• DMARDs have revolutionized the treatment of JIA, improving the quality of life for patients with joint-related disability. Since these drugs are relatively new to the market, the long-term consequences remain unknown.
  • Since many children with JIA continue to have disease as adults, patients may remain on these agents for decades, necessitating further investigation into their long-term effects.
• As DMARD and biological interventions improve, new research is showing a decrease in the percentage of the number of patients who develop long term significant or severe disability. As such, improvements in early detection and transitional care from early childhood to adolescence and into adulthood remains imperative as further improvements in care are researched.
  • Adults with JIA often have significant disability. There is a need for high quality transition of care from the pediatric to the adult population, as well as a need for studies researching this transitional population.⁶

References

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Original Version of the Topic:  

Edward Hurvitz, MD. Juvenile Idiopathic Arthritis. 11/10/2011

Previous Revision(s) of the Topic

Todd R. Lefkowitz, MD, Sean Bemanian, MD Juvenile Idiopathic Arthritis. 4/21/2016. 

Glendaliz Bosques, MD, Mani P. Singh, MD. Juvenile Idiopathic Arthritis. 7/28/2020

Author Disclosure

Olivia Tincher
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Cristina Marie Sanders, DO
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Rajashree Srinivasan, MBBS
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